Downregulation of glutathione peroxidase 3 is associated with lymph node metastasis and prognosis in cervical cancer
Authors: Zhang, Xianglan; Zheng, Zhenlong; Shen Yingji; Kim, Hyeyeon; Jin, Renshun; Li Renshu; Lee, Duo Young; Roh, Mi Ryung; Yang, Sanghwa
Glutathione peroxidase 3 (GPX3) is a member of the glutathione peroxidase family of selenoproteins and is one of the key defensive enzymes against oxidative damages to host cells. Downregulation of GPX3 due to its promoter hypermethylation has been documented in several different types of cancer, indicating that GPX3 functions as a possible tumor suppressor. In the present study, we showed that GPX3 is also significantly downregulated in cervical cancer tissues compared to normal cervical tissues by qRT-PCR analyses and immunohistostainings. GPX3 expression was significantly related to lymph node metastasis and prognosis in cervical cancer patients. Treatment of cervical cancer cells with 5-aza-2'-deoxycytidine restored the expression of GPX3 and methylation-specific PCR (MSP) confirmed the CpG methylation of the GPX3 gene. Our results indicate that promoter methylation is one of the major causes of GPX3 downregulation in cervical cancer and GPX3 could serve as a predictive biomarker for lymph node metastasis and prognosis of cervical cancer.
Resveratrol prevents the development of abdominal aortic aneurysm through attenuation of inflammation, oxidative stress, and neovascularization
Authors: Kaneko, Hidehiro; Anzai, Toshihisa; Morisawa, Maho; Kohno, Takashi; Nagai, Toshiyuki; Anzai, Atsushi; Takahashi, Toshiyuki; Shimoda, Masayuki; Sasaki, Aya; Maekawa, Yuichiro; Yoshimura, Koichi; Aoki, Hiroki; Tsubota, Kazuo; Yoshikawa, Tsutomu; Okada, Yasunori; Ogawa, Satoshi; Fukuda, Keiichi
Objective: We sought to examine the effect of resveratrol (3,4',5-trihydroxy-trans-stilbene), a plant-derived polyphenolic compound, on the development of abdominal aortic aneurysm (AAA). Methods: AAA was induced in mice by periaortic application of CaCl(2). NaCl (0.9%)-applied mice were used as a sham group. Mice were treated with intraperitoneal injection of PBS (Sham/CON, AAA/CON, n = 30 for each) or resveratrol (100 mg/kg/day) (AAA/RSVT, n = 30). Six weeks after the operation, aortic tissue was excised for further examinations. Results: Aortic diameter was enlarged in AAA/CON compared with Sham/CON. Resveratrol treatment reduced the aneurysm size and inflammatory cell infiltration in the aortic wall compared with AAA/CON. Elastica Van Gieson staining showed destruction of the wavy morphology of the elastic lamellae in AAA/CON, while it was preserved in AAA/RSVT. The increased mRNA expression of monocyte chemotactic protein-1, tumor necrosis factor-alpha, intercellular adhesion molecule-1, CD68, vascular endothelial growth factor-A, p47, glutathione peroxidase (GPX) 1 and GPX3 were attenuated by resveratrol treatment (all p < 0.05). Administration of resveratrol decreased protein expression of phospho-p65 in AAA. The increased 8-hydroxy-2'-deoxyguanosine-positive cell count and 4-hydroxy-2-nonenal-positive cell count in AAA were also reduced by resveratrol treatment. Zymographic activity of matrix metalloproteinase (MMP)-9 and MMP-2 was lower in AAA/RSVT compared with AAA/CON (both p < 0.05). Compared with AAA/CON, Mac-2(+) macrophages and CD31(+) vessels in the aortic wall were decreased in AAA/RSVT (both p < 0.05). Conclusion: Treatment with resveratrol in mice prevented the development of CaCl(2)-induced AAA, in association with reduced inflammation, oxidative stress, neoangiogenesis, and extracellular matrix disruption. These findings suggest therapeutic potential of resveratrol for AAA. (C) 2011 Elsevier Ireland Ltd. All rights reserved.